A functional immune system requires the coordinated activity of thousands of individual genes. We study transcription factors, regulatory proteins that act in the cell’s nucleus to control gene expression.
I completed my PhD at the University of Vienna Austria, where I identified a key role played by Pax5 in B cells. Following a post-doc at Cambridge University, I established a research program at WEHI focusing on immune cell differentiation. I am a Professor at the University of Melbourne and a Fellow of the Australian Academy of Science.
Throughout my career I has been intrigued the regulatory logic used by immune cells in making decisions of cell fate and particularly how transcription factors program the response. We have deciphered how factors such as BLIMP1, PU.1 and IRFs control immune cell differentiation.
We currently focus on the programming of B-cell and plasma cell diversity, as well as efforts to develop new therapies for B-cell diseases including multiple myeloma. My lab is responsible for the B-cell work in the international ImmGen Consortium.
A parallel area of interest are the dendritic cell lineages. We aim to exploit our knowledge in this area to develop a new immunotherapy approach to treat cancer.
Australia, University of Sydney, BSc (Hons), 1988
Austria, University of Vienna, PhD, 1998
2017, NHMRC Research Excellence Award (Top Ranked Project Grant)
2016, Fellow of the Australian Academy of Science
2014, Eureka Prize for Scientific Research, Australian Museum (with Hodgkin, Tarlinton, Corcoran)
2014, Professor Faculty of Medicine, Dentistry and Health services, University of Melbourne
2022-2024, Research grant, Cancer Council Victoria
2021-2023, Ideas grant, NHMRC
2020-2023, Ideas grant, NHMRC
2019-2022, Translational Research Program, Leukemia & Lymphoma Society (USA)
2019-2023, Senior Principal Research Fellow, NHMRC
Member, Immunological Genome Consortium (www.immgen.org)
Editorial Board member, Blood (2021-)
Conference organiser, Gene Expression and Signaling in the Immune System, Cold Spring Harbor, USA (2014-2020)
Conference organiser. 7th Australian B cell Dialogue. Melbourne, Australia (2019)
Chair and member, Australian Academy of Science sectional committee for new fellows (2018-2022)
Scientific program committee, International Congress of Immunology, Melbourne, 2016
Session Organizer, 14th International Congress of Immunology, Kobe Japan, 2010
Zhang S, Coughlan HD, Ashayeripanah M, Seizova S, Kueh AJ, Brown DV, Cao W, Jacquelot N, D’Amico A, Lew AM, Zhan Y, Tonkin CJ, Villadangos JA, Smyth GK, Chopin M, Nutt SL. Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT. Sci Immunol (2021) 6(58): eabf4432 PMID: 33811060.
Zhan Y, Zhang Y, Zhang S, Coughlan H, Baldoni PL, Jacquelot N, Cao WHJ, Preston S, Louis C, Rautela J, Pellegrini M, Wicks IP, Alexander WS, Harrison LC, Lew AM, Smyth GK, Nutt SL, Chopin M. Differential requirement for the Polycomb repressor complex 2 in dendritic cell and tissue-resident myeloid cell homeostasis. Sci Immunol (2021) 6(63): eabf7268 PMID: 34533976.
Fedele PL, Liao Y, Gong JN, Yao Y, van Delft MF, Low MSY, Tai L, Herold MJ, Jackson JT, Teh CE, Tan T, O’Reilly LA, Tellier J, Grigoriadis G, Huang DCS, Shi W, Nutt SL, Willis SN. The transcription factor IRF4 represses proapoptotic BMF and BIM to licence multiple myeloma survival. Leukemia (2021) 35(7):2114-2118 PMID: 33149265.
Nutt SL, Chopin M. Transcriptional Networks Driving Dendritic Cell Differentiation and Function. Immunity (2020) 52(6):942-956 PMID: 32553180.
Yoshida H, Lareau CA, Ramirez RN, Rose SA, Maier B, Wroblewska A, Desland F, Chudnovskiy A, Mortha A, Dominguez C, Tellier J, Kim E, Dwyer D, Shinton S, Nabekura T, Qi Y, Yu B, Robinette M, Kim KW, Wagers A, Rhoads A, Nutt SL, Brown BD, Mostafavi S, Buenrostro JD, Benoist C, Immunological Genome P. The cis-Regulatory Atlas of the Mouse Immune System. Cell (2019) 176(4):897-912 e820 PMID: 30686579.
Chopin M, Lun AT, Zhan Y, Schreuder J, Coughlan H, D’Amico A, Mielke LA, Almeida FF, Kueh AJ, Dickins RA, Belz GT, Naik SH, Lew AM, Bouillet P, Herold MJ, Smyth GK, Corcoran LM, Nutt SL. Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT. Immunity (2019) 50(1):77-90 e75 PMID: 30611612.
Johanson TM, Lun ATL, Coughlan HD, Tan T, Smyth GK, Nutt SL, Allan RS. Transcription-factor-mediated supervision of global genome architecture maintains B cell identity. Nat Immunol (2018) 19(11):1257-1264 PMID: 30323344.
Fedele PL, Willis SN, Liao Y, Low MS, Rautela J, Segal DH, Gong JN, Huntington ND, Shi W, Huang DCS, Grigoriadis G, Tellier J, Nutt SL. IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos. Blood (2018) 132(20):2166-2178 PMID: 30228232.
Dias S, D’Amico A, Cretney E, Liao Y, Tellier J, Bruggeman C, Almeida FF, Leahy J, Belz GT, Smyth GK, Shi W, Nutt SL. Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb. Immunity (2017) 46(1):78-91 PMID: 28099866.
Tellier J, Shi W, Minnich M, Liao Y, Crawford S, Smyth GK, Kallies A, Busslinger M, Nutt SL. Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response. Nat Immunol (2016) 17(3):323-330 PMID: 26779600.
Dendritic cells (DCs) are key sentinels that are found throughout the body and act to stimulate protective immune responses against pathogens or cancers. To better tailor the immune response to the challenge at hand, DCs have evolved into multiple anatomically and functionally distinct cell types that form an interface between the external environment and the adaptive immune system. We aim to better understand how this DC diversity is programmed on a transcriptional level as well as to devise approaches to better harness the immune stimulatory properties of DCs to promote key functions such as anti-tumour immunity.
Team members: Dr Shengbo Zhang, Angela D’Amico
Antibodies are an essential element of the immune response to infection and underpin the success of current vaccination strategies. Antibodies are produced by plasma cells, the terminally differentiated cells of the B lymphocyte lineage. We are interested in the biological process producing B lymphocytes and plasma cells, as well as the sources of diversity within the immune response. An improved understanding of the production of antibodies will not only provide new approaches to improve vaccination strategies but also provide insights into why this process sometimes goes awry, resulting in autoimmune diseases and the formation of blood cell cancers.
Team members: Dr Julie Tellier, Dr Caleb Dawson, Dr Ashley Ng, Junli Nie, Ladina Di Rago
Multiple myeloma is a malignancy of antibody-secreting plasma cells and is one of the most common blood cancers. Despite considerable treatment advances in recent years, many patients relapse, and the disease remains incurable. We aim to use genetic models and human multiple myeloma material to develop new treatment options for multiple myeloma patients.
Team members: Dr Simon Willis, Dr Melissa Holmes, Jacob Jackson
Chronic inflammatory diseases have common pathogenic features of dysregulated immune responses. However, the events leading to this dysregulation are not well understood. The maintenance of mucosal homeostasis requires sensory circuits to continually survey mucosal tracts for perturbations in microbial, dietary, and environmental cues.
In this project, we are mapping the interactions between the nervous and immune systems to establish their roles in the maintenance of tissue homeostasis and control of inflammation. An understanding of these pathways will form the basis for exploiting neuronal circuits to promote homeostatic function of immune cells and inform novel therapeutic strategies for inflammatory diseases.
Team members: Dr Cyril Seillet, Le Xiong